title: High Resolution Typing by Whole Genome Mapping Enables Discrimination of LA-MRSA (CC398) Strains and Identification of Transmission Events.
abstract: After its emergence in 2003, a livestock-associated (LA-)MRSA clade (CC398) has caused an impressive increase in the number of isolates submitted for the Dutch national MRSA surveillance and now comprises 40% of all isolates. The currently used molecular typing techniques have limited discriminatory power for this MRSA clade, which hampers studies on the origin and transmission routes. Recently, a new molecular analysis technique named whole genome mapping was introduced. This method creates high-resolution, ordered whole genome restriction maps that may have potential for strain typing. In this study, we assessed and validated the capability of whole genome mapping to differentiate LA-MRSA isolates. Multiple validation experiments showed that whole genome mapping produced highly reproducible results. Assessment of the technique on two well-documented MRSA outbreaks showed that whole genome mapping was able to confirm one outbreak, but revealed major differences between the maps of a second, indicating that not all isolates belonged to this outbreak. Whole genome mapping of LA-MRSA isolates that were epidemiologically unlinked provided a much higher discriminatory power than spa-typing or MLVA. In contrast, maps created from LA-MRSA isolates obtained during a proven LA-MRSA outbreak were nearly indistinguishable showing that transmission of LA-MRSA can be detected by whole genome mapping. Finally, whole genome maps of LA-MRSA isolates originating from two unrelated veterinarians and their household members showed that veterinarians may carry and transmit different LA-MRSA strains at the same time. No such conclusions could be drawn based spa-typing and MLVA. Although PFGE seems to be suitable for molecular typing of LA-MRSA, WGM provides a much higher discriminatory power. Furthermore, whole genome mapping can provide a comparison with other maps within 2 days after the bacterial culture is received, making it suitable to investigate transmission events and outbreaks caused by LA-MRSA.
authors.affiliation: Laboratory for Infectious Diseases and Screening, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Thijs
authors.initials: T
authors.lastname: Bosch
authors.forename: Erwin
authors.initials: E
authors.lastname: Verkade
authors.forename: Martijn
authors.initials: M
authors.lastname: van Luit
authors.forename: Bruno
authors.initials: B
authors.lastname: Pot
authors.forename: Paul
authors.initials: P
authors.lastname: Vauterin
authors.forename: Ronald
authors.initials: R
authors.lastname: Burggrave
authors.forename: Paul
authors.initials: P
authors.lastname: Savelkoul
authors.forename: Jan
authors.initials: J
authors.lastname: Kluytmans
authors.forename: Leo
authors.initials: L
authors.lastname: Schouls
mesh_terms: D000818:Animals; D015373:Bacterial Typing Techniques / Q000379:methods*; D002874:Chromosome Mapping; D004196:Disease Outbreaks; D016680:Genome, Bacterial; D058751:Livestock / Q000382:microbiology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D009426:Netherlands; D013203:Staphylococcal Infections / Q000145:classification / Q000235:genetics / Q000635:transmission / Q000662:veterinary